SALL4 deletions are a common cause of Okihiro and acro-renal-ocular syndromes and confirm haploinsufficiency as the pathogenic mechanism

Abstract

We previously reported frameshift and nonsense mutations in SALL4 in five of eight families segregating the Okihiro syndrome phenotype.⁵ A further report⁴ identified two frameshift mutations and one nonsense mutation in three affected kindreds, including the family reported by Okihiro et al.⁸ In a recent study of patients with the clinical diagnosis of Holt-Oram syndrome (OMIM No 142900), one additional frameshift mutation was reported from a family which turned out to have Okihiro syndrome rather than Holt-Oram syndrome.⁹ Furthermore, we reported three novel and one already identified SALL4 mutations in patients originally diagnosed as either Holt-Oram syndrome (later revised as Okihiro syndrome on the basis of the observation of a Duane anomaly in at least one of the affected family members in each family), acro-renal-ocular syndrome (OMIM No 102490), and Holt-Oram syndrome versus thalidomide embryopathy.¹⁰